Humoral immunity, vaccination period and demographic characteristics of first immunized smallpox vaccine recipients

General vaccination of population with vaccinia virus leaded to the eradication of smallpox, then it was finished because of the danger of adverse events. The recurrence of research interest in smallpox vaccine is due to the research of using the virus as a weapon of bioterrorism and the increased frequency of orthopoxvirus infections whereas the population immunity decline. The vaccinia virus is also used as a vector for creating recombinant vaccines. Understanding the pathway and predicting the immune response it will be able to avoid possible adverse events and excessive immunization. The aim of the study was to assess the correlations between humoral immunity, clinical signs during a vaccination period, sex and age characteristics of adults who had received several doses of vaccinia virus. We studied a vaccination clinical data of 135 subjects revaccinated with a smallpox vaccine from twice to 10 times. A total of 95% and 5% vaccine recipients experienced mild or moderate vaccination period, respectively. Inoculation skin lesions was noted at 127 subjects (94.1%). Among them more than 22% vaccine recipients experienced local or systemic adverse events. Compared to mild group moderate group had larger hyperemia (p = 0.04), scab (p = 0.01), healing time (p = 0.001). The age subjects with a moderate vaccination period is less than mild (p = 0.03), the chance of lymphadenopathy development is higher within moderate vaccination period (p < 0.001). Vaccinia neutralizing antibody titers were determined for 54 subjects using plaque reduction neutralization tests. There was a noted tendency of higher protective antibody values at women compared with men. Negative correlation between the antibody titers and the hyperemia size was revealed. Frequently axillary adenopathy is assotiated with higher protective antibody values. Vaccinia neutralizing antibody titers value are not associated with the presence and size of the lesion, the scab falling time, age and the number of previous vaccinations. The clinical variability and the immune response using the same vaccine and the same pattern vaccination would be explained by individual genetic differences that should be further explored

Association between leukocyte telomere length and specific antibody levels after vaccination against tick-borne encephalitis

The primary objective of personalized vaccination is to induce an efficient immune defense while avoiding excessive immunization. Hence, it necessitates the development of methods for predicting the magnitude of the immune response prior to vaccination. Telomere length can be considered as a promising prognostic parameter for assessing the immune response to vaccination. The aim of the work was to analyze the possible association between leukocyte telomere length and specific antibody levels after vaccination against tick-borne encephalitis. The study included 55 men and 40 women who had not previously been vaccinated against tick-borne encephalitis and had no contacts with ticks. Vaccination was carried out with the EnceVir vaccine. One month after vaccination, the level of specific IgG antibodies against tick-borne encephalitis virus was analyzed using the VektoVKE-IgG-strip test system and leukocyte telomere length was measured using real-time quantitative PCR. According to the intensity of vaccine-elicited immune responses, patients were divided into three groups: unresponsive (IgG level 0–100 IU/ml), slightly responsive (IgG level 101–200 IU/ml) and highly responsive (IgG level above 200 IU/ml). The telomere length, at least at trend level (p < 0.1), correlated with the response to vaccination as well as age, educational level and the presence of emotional stress. Using a general linear model, an association between telomere length and immune response to vaccination against tick-borne encephalitis at trend level (p < 0.1) was found only in women. Using a pairwise comparison, it was found that telomere length was significantly higher in highly responsive women than in unresponsive women. Hence, an association between leukocyte telomere length and specific antibody levels after vaccination against tick-borne encephalitis was identified in women. Therefore, peripheral blood leukocyte telomere length can be considered as a promising marker for predicting lymphocyte proliferative responses and the magnitude of vaccine-elicited cellular immune responses

ASSOCIATION BETWEEN POLYMORPHISMS IN GENES ENCODING 2′-5′-OLIGOADENYLATE SYNTHETASES AND THE HUMORAL IMMUNE RESPONSE UPON VACCINATION AGAINST TICK-BORNE ENCEPHALITIS

Vaccination forms active immunity and represents an effective way of preventing tick-borne encephalitis (TBE). However, excessive vaccination is unjustified in terms of economics and medical ethics. One of the individualized approaches to vaccines is the selection of vaccine doses depending on the expected levels of immune response. Therefore, there is a need for new methods for assessing potential human immune responses prior to vaccination. The aim of this study was to determine possible association between single nucleotide polymorphisms (SNPs) located within OAS2 and OAS3 genes, which have been previously associated with the development of severe forms of TBE, and the formation of antibodies and cytokines upon vaccination against TBE. The study involved 97 volunteers of both sexes who had not previously been vaccinated against TBE and had no contact with ticks. Venous blood samples were collected one month after vaccination against TBE using the EnceVir vaccine. Levels of specific IgG antibodies against tick-borne encephalitis virus and interleukin 4 (IL-4) were analyzed. Genomic DNA samples were genotyped for the SNPs rs2285932, rs2072136, rs1293762, rs15895 and rs1732778 in genes encoding 2’-5’-oligoadenylate synthetases OAS2 and OAS3. Antibody production in response to vaccine administration was significantly associated with SNP rs1732778 in the regulatory region of the OAS2 gene. This indicator was significantly higher in people with heterozygous genotypes G/A as compared to people with homozygous genotypes G/G and A/A. Carriers of the A allele (G/A or A/A genotypes) of the same SNP had reduced IL-4 levels as compared to the homozygous G/G individuals. Thus, the data obtained indicate that SNP rs1732778 in the regulatory region of the OAS2 gene correlates with the formation of antiviral IgG antibodies and changes in IL-4 levels upon vaccination. Evidently, the genetic polymorphism in OAS2 gene should be considered when performing individualized TBE vaccinations

Микробиом, имунная система и рак: три стороны одной медали

Purpose of the study to analyze current ideas about the relationship between the microbiota (microbiome) and the human body in the aspect of cancer pathogenesis, ambivalent character of these interactions, and the role of the immune system and immunoinfammatory status that promotes carcinogenesis or prevents neoplastic processes.Material and Methods. Literature search was carried out using Medline, Cochrane Library, Elibrary and PubMed systems, including publications over the last 7 years.Results. The microbiota includes all communities of commensal, symbiotic, and pathogenic microorganisms: bacteria, fungi, archaea, and viruses that colonize the gastrointestinal tract and other organs and tissues. The microbiome is an important factor in cancer pathogenesis due to its involvement in the basic physiological functions of the host, such as digestion, development of the immune system, and modulation of endocrine functions. In the review, the influence of microbiota of different locations (gastrointestinal tract, breast, intravaginal tract) on the development and progression of breast, colorectal and cervical cancers was discussed. The role of the microbiome in cancer pathogenesis is realized by the participation in neoplastic transformation of the epithelium, regulation of tumor progression under conditions of manifested malignant process, and modifcation of the therapeutic effect of standard drugs, including the development of original probiotic-based anticancer agents. The study of the mechanisms of action of the microbiome in the host organism opens up prospects for the development of new approaches to cancer therapy. Particular attention was paid to the mechanisms of the immunomodulatory effect of the microbiota in terms of reducing the risk of malignancy, regulating tumor progression and participating in antitumor therapy. The clinical significance of determining pathogenetically significant microbial markers associated with the aggressive form of cancer, response to treatment and toxicity of therapy was discussed. Particular attention should be paid to the potential mechanisms of interaction between cancer – microbiome – probiotics, since the latter can provide modification of malignancy processes, exert an antitumor effect, and modulate the effectiveness of drug therapy. The feasibility of editing the microbiota by probiotics was considered, and antitumor properties (effects) of bacteria and strategies for modifying the microbiome for the prevention and treatment of cancer were discussed. Цель исследования ‒ анализ современных представлений о взаимоотношениях микробиоты (микробиома) и организма человека в аспекте изучения патогенеза злокачественных новообразований, амбивалентного характера этих взаимодействий, роли иммунной системы и иммуновоспалительного статуса, способствующего канцерогенезу или препятствующего неопластическим процессам.Материал и методы. Поиск литературы производился в системах Medline, Cochrane Library, Elibrary и Pubmed, включались публикации, характеризующие современные результаты (глубиной около 7 лет).Результаты. Микробиота содержит в себе все сообщества комменсальных, симбиотических и патогенных микроорганизмов: бактерии, грибки, археи и вирусы, которые колонизируют желудочно-кишечный тракт и другие органы и ткани. Микробиом является важным фактором в патогенезе злокачественных новообразований в связи с участием в таких базовых физиологических процессах хозяина, как пищеварение, развитие и поддержание динамического баланса иммунной системы и модуляция эндокринных функций. Обсуждается влияние микробиоты разной локализации (желудочно-кишечного тракта, молочной железы, интравагинального тракта) на развитие и прогрессирование злокачественных опухолей молочной железы, колоректального рака (КРР) и рака шейки матки (РШМ). Роль микробиома в патогенезе злокачественных новообразований реализуется в: участии в неопластической трансформации эпителия; регуляции опухолевой прогрессии в условиях манифестированного злокачественного процесса; модификации терапевтического эффекта стандартных лекарственных препаратов, а также разработке оригинальных противоопухолевых агентов на основе пробиотиков. Изучение механизмов действия микробиома в организме хозяина открывает перспективы разработки новых подходов терапии рака. Особое внимание уделено механизмам иммуномодулирующего эффекта микробиоты в снижении риска малигнизации, регуляции опухолевой прогрессии, участии в противоопухолевой терапии. Обоснована клиническая целесообразность определения патогенетически значимых микробных маркеров, связанных с агрессивностью злокачественного процесса, ответом на лечение и токсичностью терапии. Особо следует обратить внимание на потенциальные механизмы взаимодействия оси рак – микробиом – пробиотики, поскольку последние могут обеспечивать модификацию процессов малигнизации, оказывать противоопухолевое действие и модулировать эффективность лекарственной терапии. Рассматриваются возможности редактирования микробиоты пробиотиками, противоопухолевые свойства (эффекты) бактерий и стратегии модификации микробиома для профилактики и лечения онкозаболеваний.

Варианты полиморфных изменений генов р53, XRCC1 и XPD у детей с острым лимфобластным лейкозом

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Analysis of Vaccinal Process Peculiarities in Persons Immunized with Smallpox Live Vaccine in Case of Primary Vaccination and Revaccination

Immunization against smallpox may be attended by serious complications. The premises for the differences in postvaccinal reaction intensity are underexplored. In this paper presented is the review of peculiarities of postvaccinal manifestations in members of the Russian population primarily immunized against smallpox as compared to the revaccinated ones. Examined has been the cohort of 217 people, of whom 82 are vaccinated initially, and 135 - repeatedly within the period from 2000 to 2013. Average age of the vaccinated is 40.0 years (ranged 20 to 40). Studied has been severity of vaccine-challenged condition and cutaneous inflammatory vaccinal elements. In case of initial vaccination medium severity has been observed 2.1 times oftener than low one. In case of revaccination - low level of severity has been registered 17.7 times more frequently than the medium one. Hyperemia zone is 2.2 times greater as regards primary vaccination compared to revaccination, zone of induration - 1.9 times. The diameter of the sore is 1.3 and its shedding time is 1.4 times greater and longer, respectively. Thus, initial vaccination follows more severe course and is attended by expressed response in comparison to booster one